title: X-ray crystal structure of the UCS domain-containing UNC-45 myosin chaperone from Drosophila melanogaster.
abstract: UCS proteins, such as UNC-45, influence muscle contraction and other myosin-dependent motile processes. We report the first X-ray crystal structure of a UCS domain-containing protein, the UNC-45 myosin chaperone from Drosophila melanogaster (DmUNC-45). The structure reveals that the central and UCS domains form a contiguous arrangement of 17 consecutive helical layers that arrange themselves into five discrete armadillo repeat subdomains. Small-angle X-ray scattering data suggest that free DmUNC-45 adopts an elongated conformation and exhibits flexibility in solution. Protease sensitivity maps to a conserved loop that contacts the most carboxy-terminal UNC-45 armadillo repeat subdomain. Amino acid conservation across diverse UCS proteins maps to one face of this carboxy-terminal subdomain, and the majority of mutations that affect myosin-dependent cellular activities lie within or around this region. Our crystallographic, biophysical, and biochemical analyses suggest that DmUNC-45 function is afforded by its flexibility and by structural integrity of its UCS domain.
authors.affiliation: Department of Biology, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182-1030, USA.
authors.forename: Chi F
authors.initials: CF
authors.lastname: Lee
authors.forename: Arthur V
authors.initials: AV
authors.lastname: Hauenstein
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Fleming
authors.forename: William C
authors.initials: WC
authors.lastname: Gasper
authors.forename: Valerie
authors.initials: V
authors.lastname: Engelke
authors.forename: Banumathi
authors.initials: B
authors.lastname: Sankaran
authors.forename: Sanford I
authors.initials: SI
authors.lastname: Bernstein
authors.forename: Tom
authors.initials: T
authors.lastname: Huxford
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000737:chemistry; D004926:Escherichia coli; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009218:Myosins / Q000378:metabolism; D018583:Pliability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D053838:Scattering, Small Angle; D016415:Sequence Alignment
chemical_list: D051186:Armadillo Domain Proteins; D029721:Drosophila Proteins; D018832:Molecular Chaperones; D011994:Recombinant Proteins; C550552:UNC-45 protein, Drosophila; D009218:Myosins